PMID- 33613105 OWN - NLM STAT- MEDLINE DCOM- 20220114 LR - 20220114 IS - 1449-2288 (Electronic) IS - 1449-2288 (Linking) VI - 17 IP - 2 DP - 2021 TI - 17beta-Estradiol promotes LC3B-associated phagocytosis in trained immunity of female mice against sepsis. PG - 460-474 LID - 10.7150/ijbs.53050 [doi] AB - Sepsis is a common serious clinical infectious disease accompanied by more severe injuries and higher mortality rates in men than women. The much higher level of 17beta-estradiol (E(2)) in female is one of the significant reasons for better sepsis resistance ability. Trained immunity is a novel way to fight against infection by improving innate immunity. However, whether beta-glucan-induced trained immunity can promote macrophage phagocytosis to clear infections in early sepsis has not been clarified. And whether E(2) involved in this process needs further investigation. Symptoms among male, female and ovariectomized (OVX) C57BL/6 mice in early sepsis were detected. The effect of trained immunity on macrophage LC3B-associated phagocytosis (LAP) and the mechanism of E(2) functioned in this process have also been explored. We demonstrated compared with male mice, female has significantly more mild symptoms and more reactive oxygen species (ROS) production and stronger NADPH oxidase 2 (NOX2) expression in the macrophage of major organs. In contrary, these characteristics are disappeared in OVX mice. Furthermore, in macrophage cell lines and primary bone marrow- derived macrophages (BMDMs), beta-glucan-induced trained immunity can increase ROS production by activating NOX2 to promote macrophage LAP. E(2) can up-regulate RUBICON through estrogen receptor alpha (ERalpha) to further facilitate macrophage LAP. These results indicated that trained immunity can improve sepsis resistance ability by stimulating macrophage LAP. E(2) can boost ROS production and RUBICON expression to further promote macrophage LAP, which can provide a new perspective to recognize the mechanism of trained immunity in gender differences when responding to sepsis. CI - (c) The author(s). FAU - Sun, Zhiheng AU - Sun Z AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Qu, Junxing AU - Qu J AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Xia, Xiaoyu AU - Xia X AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Pan, Yuchen AU - Pan Y AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Liu, Xinghan AU - Liu X AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Liang, Huaping AU - Liang H AD - State Key Laboratory of Trauma, Burns and Combined Injury, Department of Wound Infection and Drug, Daping Hospital, Army Medical University, Chongqing, China. FAU - Dou, Huan AU - Dou H AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. AD - Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, China. FAU - Hou, Yayi AU - Hou Y AD - The State Key Laboratory of Pharmaceutical Biotechnology, Division of Immunology, Medical School, Nanjing University, Nanjing, China. AD - Jiangsu Key Laboratory of Molecular Medicine, Division of Immunology, Medical School, Nanjing University, Nanjing, China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210101 PL - Australia TA - Int J Biol Sci JT - International journal of biological sciences JID - 101235568 RN - 4TI98Z838E (Estradiol) SB - IM MH - Animals MH - Estradiol/*pharmacology MH - Female MH - *Immunity MH - Mice MH - *Phagocytosis PMC - PMC7893586 OTO - NOTNLM OT - LAP OT - ROS OT - RUBICON OT - estradiol OT - sepsis OT - trained immunity COIS- Competing Interests: The authors have declared that no competing interest exists. EDAT- 2021/02/23 06:00 MHDA- 2022/01/15 06:00 PMCR- 2021/01/01 CRDT- 2021/02/22 05:52 PHST- 2020/09/09 00:00 [received] PHST- 2020/12/02 00:00 [accepted] PHST- 2021/02/22 05:52 [entrez] PHST- 2021/02/23 06:00 [pubmed] PHST- 2022/01/15 06:00 [medline] PHST- 2021/01/01 00:00 [pmc-release] AID - ijbsv17p0460 [pii] AID - 10.7150/ijbs.53050 [doi] PST - epublish SO - Int J Biol Sci. 2021 Jan 1;17(2):460-474. doi: 10.7150/ijbs.53050. eCollection 2021.